Dopamine ups and downs in vulnerability to addictions: a neurodevelopmental model

Abstract

Addictions are commonly presaged by problems in childhood and adolescence. For many individuals this starts with the early expression of impulsive risk-taking, social gregariousness and oppositional behaviors. We propose here that these early diverse manifestations reflect a heightened ability of emotionally salient stimuli to activate dopamine pathways that foster behavioral approach. If substance use is initiated, these at-risk youth can also develop heightened responses to drug-paired cues. Through conditioning and drug-induced sensitization, these effects strengthen and accumulate, leading to responses that exceed those elicited by other rewards. At the same time, cues not paired with drug become associated with comparatively lower dopamine release, accentuating further the difference between drug and non-drug rewards. Together, these enhancing and inhibiting processes steer a pre-existing vulnerability toward a disproportionate concern for drugs and drug-related stimuli. Implications for prevention and treatment are discussed.

Joint statement on dual disorders: Addiction and other mental disorders

“…Current scientific evidence shows that addiction and a co-occurring mental disorder are not separate disorders, but rather different, interacting, clinical conditions. They may occur simultaneously or sequentially, and may develop due to individual and environmental factors (Leyton & Vezina, 2014;Szerman & Martinez-Raga, 2015). 6.…”

Addiction, Experimental Models and Neurobiological Mechanisms

“…A relationship has been clearly established between the activation of this meso-corticolimbic system and the release of dopamine in its target zones. [18,19] With the progress in imagery, in microdialysis experiments in animals and more recently in humans it has also been shown that all the substances described as "artificial paradises" are able to activate this pathway and trigger the release of dopamine. For instance, a link has been clearly established between the inducement of a euphoric effect by amphetamines and the release of dopamine it produces.…”

What’s deficient in reward deficiency?

“…26 The basis and meaning of these low DA responses, however, remain unclear. They could reflect neurotoxic effects in late-stage addictions, 27 heritable endophenotypes, conditioned inhibitory effects induced by cues that signal the absence of reward, 5,28 or some combination of these effects (e.g., initial predispositions aggravated by rapidly developing conditioned effects and laterstage neurotoxicity).…”

“…5,28 In comparison, augmented striatal responses have been seen when high-risk individuals are tested in the presence of drug-paired cues. 5,13,28 Indeed, across stages of addiction, striatal DA release is induced by drug-paired cues alone.…”

“…5,13,28 Indeed, across stages of addiction, striatal DA release is induced by drug-paired cues alone. 5,28,29 Thus, although the full clinical picture of addiction may well include periods of both increased and decreased DA transmission, the appearance of drug-related cues can provoke DA release, transforming a low DA state into a high one, fostering impulsive actions 30 and drug-seeking behaviours.…”